The purpose of these studies is to maximize the effectiveness of cardiopulmonary resuscitation (CPR) in humans. The work includes: (1) The first detailed hemodynamic studies of external chest compression in humans. Using aortic, right atrial, and wedged bronchial pressures, and the hemodynamic response to changes in compression rate and compression duration, we expect to be able to identify the contribution of intrathoracic (pleural) pressure fluctuation or, alternatively, direct cardiac compression, to the mechanism of blood flow during CPR in humans. (2) Maximization of coronary perfusion pressure during external chest compression in humans by manipulation of compression rate and compression duration. (3) Characterization of coronary pressure-flow relationships by use of radiolabeled microspheres in brain dead subjects undergoing CPR. (4) A trial in humans of CPR with a pneumatic vest. In animal studies the vest has generated higher pressures and flows with less trauma and greater survival than conventional CPR. (5) Measurements of airflow out of the lungs and pressures in different positions in the airway (trachea, bronchi, bronchioles) and thorax in order to test the hypothesis that chest compression with an unobstructed airway raises intrathoracic pressure by collapsing airways and trapping air in the lung. (6) The exploration of a pharmacologic means of maximizing myocardial oxygen supply-demand balance during ventricular fibrillation at the low perfusion pressures characteristic of CPR by selective administration of epinephrine phenylephrine, and calcium antagonists. This approach will be evaluated by 31P NMR spectroscopic measurement of high energy phosphate content and pH, myocardial perfusion and oxygen consumption, and left ventricular function after defibrillation. These studies are a natural extension of a decade of research in CPR in this laboratory. This work has elucidated the mechanism of blood flow during external chest compression, the determinants of cerebral and myocardial perfusion during CPR, the mechanism by which epinephrine promotes resuscitation, and developed and tested new methods of resuscitation.